This invention relates generally to analytical detection of target molecules with probe molecules, and more specifically to extending the shelf life and stability of analytical probes under ambient or packaged conditions.
Biological systems, and in particular biomolecules from these systems, have a remarkable ability to recognize specific target analytes within complex mixtures. This specificity has been exploited for the manufacture of analytical devices having biomolecule probes that allow detection of target analytes in a variety of test samples. Specific analytes can be individually detected in samples that are very complex with respect to the presence of contaminants or other analytes including, for example, synthetic reaction mixtures, environmental samples, or tissue or fluid samples obtained from individuals. Microarray technology uses analytical detection devices having thousands of biomolecules for the simultaneous analysis of entire ensembles of target analytes in complex systems. Microarray technology using nucleotide probes is routinely used for a variety of important applications including, for example, genome-wide quantitative analysis of gene expression and large-scale single nucleotide polymorphism (SNP) discovery and genotyping.
Microarrays are also beginning to play a role in the reinvention of cancer classification and drug discovery. Importantly, microarray technology has allowed investigators to progress from studying the expression of one gene in several days to hundreds of thousands of genes simultaneously in a matter of hours. Since cancer is a product of aberrant expression for large sets of genes, microarray technology is revolutionizing cancer diagnosis. Accordingly, large sets of genes, whose patterns of expression detect the presence of cancer, identify tumor type or characterize a unique property of a tumor, can be evaluated to determine a diagnosis or prognosis of a cancer patient. For example, gene expression profiling using microarrays has been demonstrated to distinguish tumor type and provide insight on clinical outcome for several cancers including lymphomas and leukemias.
Microarray technology is also useful for monitoring gene expression in premalignant and tumorigenic cells following exposure to anticancer agents. Thus, in a research setting microarray technology can be used in conjunction with known anticancer agents to identify better, specific markers for cancer diagnosis, prognosis and treatment. Microarray technology can also be used in a research setting to evaluate candidate anticancer drugs. For example, the effect that a candidate anticancer agent has on gene expression patterns in a cancerous cell can be used to determine the mechanism of action of pharmaceutical agents or potential adverse outcomes for the development of safer and more efficacious drugs. Similar analytical procedures can also be carried out in a clinical setting with biopsies from cancer patients in order to predict onset of unwanted side effects or other adverse events before they occur to the detriment of the patient.
Microarray technology can also be used to monitor environmental exposure to chemicals in humans. Again, because exposure to pathogens or hazardous chemicals causes global changes in gene expression, alterations in microarray expression profiles can be used to determine the nature and level of exposure to hazardous chemicals. Monitoring exposure to chemicals and pathogens can be useful in a variety of settings including, for example, occupational health such as manufacturing facilities in which there is a risk of exposure to chemicals used in the manufacturing process, security checkpoints such as airports or government buildings or battle zones such as those in which combatants may be exposed to biological warfare agents or chemical warfare agents.
Microarrays and other analytical devices that rely on biomolecule probes, and other sensitive probes, are susceptible to degradation in several conditions of storage, transportation and use. Such degradation can lead to a reduction in sensitivity or even an increase in the risk of incorrect diagnosis due to artifacts. Although it is possible to avoid degradation in some cases by minimizing contact of a microarray to such conditions, many applications that would otherwise benefit from use of a microarray are precluded. For example, inability of microarrays to survive storage and transportation conditions post manufacturing can compromise or even preclude their use in some field, laboratory or clinic locations.
Thus, there exists a need for methods of increasing the stability of probe arrays under typical conditions of storage and/or use. The present invention satisfies this need and provides other advantages as well.